Cocaine dependence involves profound alterations in functional networks that subserve motivation, associative learning, memory and cognitive control. Neuroimaging modalities have improved our understanding of the neuropathology associated with chronic cocaine use. The spatial correlations of spontaneous hemodynamic brain activity (obtained through blood oxygenation level dependent functional magnetic resonance imaging, BOLD fMRI) define statistical maps that are strikingly convergent with known or hypothesized functionally connected circuits. We have developed methods to systematically apply this approach of functional connectivity in two brain areas centrally implicated in drug addiction, anterior cingulate cortex (ACC) and basal ganglia (BG) of healthy volunteers. Functional connectivity statistical maps are stable across individuals and across time, and have been shown to be useful in delineating novel loci of neuronal dysfunction in other psychopathologic conditions. We propose to apply this approach in 30 cocaine-dependent individuals who will be compared to a matched subset of non-dependent healthy comparisons that we have already scanned on the same 3.0 Tesla Siemens Allegra. We hypothesize that cocaine-dependent individuals will exhibit decreased functional connectivity, particularly between ventral striatum and rostral (limbic) ACC. Accordingly we will examine functional connectivity of ACC and BG in cocaine addicted individuals (abstinent for 2-8 weeks) in comparison with already scanned healthy non-dependent subjects who will be matched for age, sex, and handedness. We hypothesize that the strength of functional connectivity between ventral striatum and BA25 will be positively related to fractional anisotropy within the same circuit. For this purpose, we propose to obtain 29-direction diffusion tensor imaging (DTI) scans in the cocaine-dependent subjects. In addition to testing hypotheses concerning the impact of cocaine addiction on the FC of neural circuits associated with the ACC and BG, the proposed study will determine the extent to which these two parameters, which are hypothesized to index a common neurophysiological basis, are related in this clinical population. This project will lay the groundwork for future studies that will examine the clinical implications of decreased connectivity with respect to prediction of relapse, mood comorbidity, and cognitive rehabilitation. Cocaine dependence remains a serious public health problem. We have developed techniques for defining brain circuitry by observing patterns of correlated brain activity that we believe can also be related to methods useful for tracing the white matter connections between neurons. We propose an initial one-year study to validate our methods in a newly collected sample of cocaine dependent adults, to compare to already collected data from healthy comparison subjects. This project will provide the basis for future studies. [unreadable] [unreadable] [unreadable]